Eye (1990) 4, 79-88
Peculiar Ophthalmic Proliferations JOAN MULLANEY Dublin, Ireland
Summary Six unusual cases diagnosed by various scientific methods are described to highlight the role of the histopathologist in clinical ophthalmology. The first case shows the importance of fast tissue diagnosis to prevent possible radical treatment in a limbal pseudotumour. The second presentation is of a small conjunctival mass with orbital involvement, immunohistochemically a B-cell lymphoma and occurring after a recent testicular tumour. The third patient presented with the rarely described nod ular hypersensitivity conjunctivitis (Splendore-Hoeppli reaction) and it is suggested that these ophthalmologically observed asymptomatic lesions are apparently clini cally transient so reports may be few because of infrequent biopsy. Pan-uveal melan ocytic tumours concurrent with thoracic or abdominal carcinoma are reviewed.
DNA flow cytometry could, perhaps, assess those ocular lesions for malignancy. The fourteenth case in the literature of lacrimal sac melanoma and possibly the first by tear seedling is illustrated. Lastly, a paediatric orbital fibrous histiocytoma is a cautionary anecdote with successful outcome.
I am very honoured to be chosen as the 4th European Guest Lecturer. I felt that I would take rare and interesting clinical ophthalmo logical conditions and illustrate the role of a histopathologist in their identification. Most of the cases described presented as space occupying lesions which, on microscopic examination, showed a wide variety of path ological reaction, with often an obscure aetiology. Management and prognosis where relevant are discussed. Firstly, three interesting conjunctival pro liferations are presented. Case Reports
(1) A 64 year old farmer was referred with a history of a sore red eye for seven months and of having had 'grit' removed by the local nurse, in the left eye 18 months pre-
viously following shaking straw. Vision was normal. On clinical examination there was a raised hard ridge of tissue above the limbus extending from 8 o'clock to 2 o'clock, with hyperaemia of the overlying and upper bulbar conjunctiva. No foreign body was demon strated on radiological examination. In view of the extent of the lesion and its consistency, carcinoma was considered a definite possi bility. A biopsy with frozen section control was proposed and, if positive, enucleation should follow. However, the patient refused enucleation. An excision biopsy was per formed. Histopathology of the small piece of tissue showed a chronic inflammatory lesion with fibroblasts sometimes in fascicular arrangement with many plasma cells and many eosinophils. The overlying conjunctival epithelium had undergone squamous meta-
European Guest Lecturer, Oxford Ophthalmological Congress, July,
1989.
Correspondence to: National Ophthalmic Pathology Laboratory & Registry of Ireland, Royal Victoria Eye & Ear Hospital, Adelaide Road, Dublin 2, Ireland.
80
Fig. 1
JOAN MULLANEY
Case 1. Limbal pseud otumour. (Courtesy of Mr Maurice Fenton)
plasia. The specimen was serially sectioned but no foreign body, fungus helminth or seed husk remnant could be identified. Malignancy was not found. This was an example of limbal pseudotumour with severe chronic inflam mation and architectural changes suggestive of fibrous histiocytoma. Three months later there was still some minor thickening and slight congestion. However, after eight years there is only a minute scleral scar at approxi mately 10 o'clock, in a white eye (Figs. 1 and 2). The case is presented to indicate the importance of the invocation of frozen sec tions examination during operation for the assessment of a large suspicious limbal lesion if enucleation is contemplated. (2) A 66 year old man presented with a left conjunctival nodule in July, 1988 and a history of orchidectomy in April, 1988 for seminoma. The conjunctival biopsy revealed itself to be a lymphomatous condition and, with histo chemistry, it was evident that it was a small B-celilymphoma. A month after the conjunc tival lesion he was referred to the orbital clinic with progressive downward displacement of
the left globe. A transeptal biopsy showe� that he now had a lymphoma (small B ce� type) occupying the upper temporal quadranV of the orbit. In view of the rarity of primary orbital lymt phomas his testicular biopsy was re-evaluated and the diagnosis was revised from that of seminoma to lymphoma (Fig. 3). He was referred to the Oncology unit and a full cr scan and bone marrow aspirate were normal. He was commenced on combination therapy BACOP/Bleomycin, Adriamycin, Cyclo phosphamide, Oncovin (Vincristin), and Pre dnisolone with six courses in all. The orbital lesion clinically resolved after four of the six courses. At the time of writing he is appar ently well. In this patient histopathology and histochemistry were important. The latter was used to re-evaluate the conjunctival, orbi tal and testicular lesions. The monoclonal markers, namely the common leucocyte anti gen (CLA) reliably marking 90% of the B cells identified in this case, can be done on paraffin sections. Placental leucocyte acid phosphatase (PLAP) (positive in seminoma)
PECULIAR OPHTHALMIC PROLIFERATIONS
Fig. 2
81
Case 1. Scar eight years after surgery.
was negative in the testicular, conjunctival and orbital lesions. This case is of consider able interest as seminoma histologically may resemble a lymphoma but treatment differs from that of a seminoma. (3) A 39 year old male patient had bilateral recurring dendritic ulcers from childhood which were quiescent. A routine examination in July 1983 showed small white nodules on the left bulbar conjunctiva underneath the upper lid with some hyperaemia (Fig. 4). After excision biopsy of these nodules he received chloromycetin ointment three times a day for a week. Histological examination of the nodules showed eosinophilic necrosis (Fig. 5) surrounded by epithelioid and mono nuclear cells with occasional giant cells of Langhan's type, numerous eosinophils as well as some plasma cells and lymphocytes. One month later two nodules reappeared. They were once again treated with chloromycetin and subsided. On 15 February 1984 the patient was seen with a similar nodule on the right conjunctiva which also regressed on treatment.
These findings conform to the hypersensi tivity reaction known as the Splendore Hoeppli phenomenon first described in the bulbar conjunctiva and well summarised by Ashton and Cook. I The eponyms arise from Splendore2 working in Brazil who described this reaction with a pulmonary fungus and Hoeppli3 in China who observed it with schistosoma ova. There is a slight air of des peration in the search for the causative agent of the rather typical histology. Bacteria (strep tococci), fungi, helminths, viruses, chlamydia trachomatis and even insects (warble fly) have been incriminated. The patient illustrated here had a long corneal herpetic history with treatment and the conjunctival nodules, never limbal, were apparently intermittent and causing no particular clinical disturbance. Case reports are extremely rare in the liter ature but discussions with numerous ophthal mologists would indicate that (a) these nodular proliferations are clinically not infre quently seen, (b) they may be asymptomatic, (c) hyperaemia can be slight, and (d) they seem to retrogress. The presence of numerous
82
Fig. 3
JOAN MULLANEY
Case 2. Testicular tubules with lymphomatous infiltration.
eosinophils suggests a hypersensitivity reac tion of as yet undetermined aetiology. Further studies are necessary to assess if this condition is of any real clinical significance when the aetiology is unknown or whether it is merely a passing pathological curiosity. Actinic granuloma has similar microscopic findings to the Splendore-Hoeppli phenom enon but there are no eosinophils. Swimming pool granuloma with marked injection of the conjunctiva caused by mycobacterium marinum is another histological differential diagnosis, but the organisms can be demon strated in the lesions. It sometimes imitates Parinauds ocular glandular syndrome. Next, problems relating to the melanocytic system will be considered. The vast literature on the pathology of the ocular pigmentary apparatus might suggest that the emergence of still obscure melan ocytic lesions would be unlikely, but interest ing facets can still be discovered. For example, free DNA was seen by light micro scopy in two necrotic choroidal melanomas4 in the form of lakes confirmed as being DNA by transmission electron microscopy and show-
ing a direct continuity between a lake and the nuclear chromatin. Jensen (personal com munication 1989) had not found DNA in mel anomas again. I have observed it in two specimens (Fig. 6). No other reports to date have appeared which is surprising in view of the common occurrence of necrotic uveal melanomas. The distribution of this free DNA in melanoma appears to differ from that found in retinoblastoma. An ultrastructural examination was found to be necessary to demonstrate the presence of small discrete electron dense DNA granules 60-200 nm in retinoblastoma.5 These deposits have an affin ity for collagen and basal lamina, especially in the iris and they were not phagocytosed by trabecular endothelial cells. Examination by transmission electron microscopy of the anterior segment in globes containing nec rotic uveal tract melanoma may give findings analogous to those found in retinoblastoma for free DNA deposition. DNA in tumours can be measured by flow cytometry. A comparison of nuclear/nucleo lar size in melanoma cells can be measured by allowing the nuclei, stained with a fluorescent
PECULIAR OPHTHALMIC PROLIFERATIONS
Fig.4
83
Case 3. Hypersensitivity nodular conjunctivitis (Splendore-Hoeppli phenomenon). Courtesy of Dr. Denis
Wilson. dye, to flow past a laser beam and the result
Retrospective studies by flow cytometry for
ing light emanations are plotted on a histo
ploidy abnormalities might be used to study
gram.6 This method can be used on paraffin
the pathological material from the eight cases
and retrospective studies are therefore poss
reported from 1966 to 19859-12 of a new syn
ible. Fresh specimens give more sensitive
drome with diffuse bilateral uveal melan
readings. Normal cells have a diploid comple
ocytic lesions and concurrent abdominal or
ment of DNA, ie two each of the autosomes
thoracic carcinomas. This is suggested as
but most tumour cells may be aneuploid with
there appears to be disagreement using light
increased numbers of chromosomes.
The
microscopic methods of examination on the
more aneuploid the tumour the worse the
enucleated specimens as to whether these rare
prognosis in melanomas. Ploidy abnormali
uveal tract lesions are naevi or melanomas (de
ties correlated with survival better than the
Wolff-Rouendaal, 1989 personal communica
usual histological parameters.7 However, in
tion). Six of the eight reported cases pre
contra distinction to melanomas large retino
sented first with increased visual loss but on
blastomas are said to have a normal ploidy
subsequent examination were found to have
level and this analytical method did not offer
information either about risk of metastases or
malignant epithelial tumours of pancreas, large intestine, lung, ovary and gall bladder.
the degree of anaplasia8 in these tumours. The
A general autopsy was performed on four
reasons for this are not understood and
patients but all eight cases had eyes studied
further analysis is necessary.
microscopically. The primary malignancy was
84
Fig.S
JOAN MULLANEY
Case 3. Histology eosinophilic necrosis with giant cells.
the cause of death. A 60 year old patient which we described13 had bilateral lens opac ities, left iris protrusion, macular elevation, patchy fluorescence and irregular fundal pig mentation
on
presentation.
After
three
months vision was reduced to hand move ments. There was rubeosis and extensive ret inal detachments. The patient
developed
in the literature of bilateral uveal malignant melanomas" and diffuse malignant melan omas are very rare14 and bilateral ocular car cinomatous metastases were uncommon in 10
of 196 eyes containing metastases.1S Further case descriptions are awaited with interest. Precancerous melanosis, classified under primary acquired melanosis by the W HO
disseminated intra-vascular coagulation and
group16 usually invokes a lively discussion
died. Ocular histopathology, post mortem,
about
showed diffuse pan uveal melanomata with an
patient with
occasional mitosis. Only one globe of the
multiple melanomata developed a very rare
reported cases was examined by transmission
complication.
electron
microscopy.
Melanosomes
microscopy
and
management.
precancerous
A
melanosis and
were
A 65 year old healthy man (normal vision)
identified in the lesions. The histopathology
presented in 1977 with a pigmented spot of
was most suggestive of melanoma and the
five years' duration under his right lower lid.
secondary effects on the globe were those of a
rapidly proliferating lesion. The differential diagnoses of these unusual ocular changes are
It was excised and was histologically a con junctival melanoma. During the next 11 years he had five other melanomata removed from
bilateral pigmented lesions on the fundus,
different lid and bulbar sites. Exenteration
bilateral hypertrophy of the pigment epithe
was contemplated but was decided against in
lium, toxic retinopathy, diffuse uveal malig
1981. He received chemotherapy in 1985.
nant
Epistaxis occurred in December 1988. He was
melanoma,
reactive
lymphoid multiple
admitted in January 1989 for exploration of
melanocytomas, metastatic disease or reticu lum cell sarcoma. 10 There are only 18 reports
the lacrimal sac where there was a hard black
hyperplasia,
leukemic infiltrates,
nodule filling the sac and involving the can-
85
PECULIAR OPHTHALMIC PROLIFERATIONS
Fig. 6
DNA 'lakes' in necrotic melanoma.
aliculus. This mass appeared to be a tumour
lacrimal sac. Thus, Blake and Mullaneyl8
and excision of lacrimal sac, canaliculi, naso
reported the fifth case of mucoepidermoid
lacrimal duct and medial and canthal liga
carcinoma at this site. The previous reports
ments were performed. Histology showed a
were two cases from Brazil19 and two cases
heavily pigmented poorly differentiated nec
from China.20 The incidence of mucoepider
rotic melanoma with extension into the neigh
moid carcinoma may be much greater than
bouring muscle. Serial sections failed to show
the literature indicates. A faulty diagnosis of
extension from conjunctiva. Ear, nose and
transitional cell carcinoma may frequently
throat examination showed nothing abnormal
have been made. Simple histochemical stains
in these cavities. At the time of writing his
for mucin can help to differentiate and this
right VA is
with good
can be further confirmed by transmission elec
closure of the lids. When he presented with
tron microscopy. Mucoepidermoid carcinoma
this last lesion he had conjunctival melanosis
carries a worse prognosis than the others at
but no tumour and it is postulated that this is
this region and exenteration is said to be the
either a new tumour arising in the lacrimal sac
procedure of choice in these cases.
6/24,
left VA is
6/9
from residual primitive melanin producing
Finally, the importance of accurate histo
cells developing in the sac during fetal ecto
pathological diagnosis in relation to an orbital
dermal downgrowth or a secondary seedling
tumour is demonstrated by the following
perhaps carried in by tears. Only 13 c�ses17 of
patient whom I presented at the 1978 Meeting
primary melanomas in the lacrimal sac have
of
been reported but these patients did not have
Society in view of the importance of the diag
precancerous melanosis. This would appear
nosis and of its rarity and a thirteen year fol
to be the fourteenth lacrimal sac melanoma
low-up can now be reported.21
and to be the first recorded in precancerous melanosis perhaps from a tear seedling. Other rarities may still be discovered in the
the
European
Ophthalmic
Pathology
A two year old girl had a swelling medial to her left eye which was said to have been pres ent since birth. She had mild proptosis,
86
JOAN MULLANEY
Fig. 7
Lacrimal sacfilled with melanoma.
normal vision and left optic disc swelling. Investigation indicated that she had an invas
comata or a metastases from an embryonal tumour enter as important differential diag
ive orbital tumour which, at surgery, was
noses if the patient is a child. Fibrous his
found to enter the ethmoid and nasal regions.
tiocytoma is extremely rare in infants and
The histological diagnosis was orbital fibrous histiocytoma. She had two recurrences at the
children. Our case appears to be the youngest ever diagnosed at that time in mid
1978 but
with chemotherapy. She is now fifteen years of
earlier that year a single case was recorded in a one year old child.22 An analysis of 150 cases
age. She has no epiphora,
of orbital fibrous histiocytoma had patients
age of three and eight years treated by surgery
5 mm of enophthal
mos, 4 mm of globe depression and normal ocular movements. VA right is
6/5,
left
6/12
ranging from four years of age upwards and·
the median was 43 years. 23 A single case of this
with slight left optic disc deformity. This case
tumour in a nine month old infane4 required.
illustrated very well the emphasis which must
ultrastructural
be put on accurate histopathological diagnosis in the management of this tumour. This girl,
and
immunohistochemical
studies, demonstrating the presence of vimen tin to distinguish the lesion from juvenile xan
now thirteen years after initial surgery for her
thogranuloma and eosinophilic granuloma
definitely invasive growth, appears still to be free of tumour. 21
derives from undifferentiated mesenchymae
Rhabdomyosarcoma, other soft tissue sar-
and the stem cells differentiate into fibroblasts
(histiocytosis
X).
Fibrous
histiocytoma
PECULIAR OPHTHALMIC PROLIFERATIONS
or histiocytes. This parentage may yield a wide range of histological findings both by light
microscopy,
transmISSIOn
electron
microscopy and immunohistochemistry and cause considerable confusion in the final diagnosis. The assessment of malignancy in fibrous histiocytoma can be difficult and may require sophisticated immunohistochemistry though even these findings are debatable. 23 Complete excision of the benign entity which is frequently locally invasive should be done while exenteration is recommended for cQn firmed malignant forms.22 Conclusion
This paper describes six cases of rare clinical aI)d pathological interest and contains cau tionary anecdotes. The material has been used to illustrate the necessity for the close liaison between ophthalmologists and pathol ogists in this field. Standard biopsy tissue
using light microscopy still yields the basic diagnosis in nearly all instances. The use of transmission electron microscopy to elucidate lesions, notably in the tumour area, c
Peculiar Ophthalmic Proliferations JOAN MULLANEY Dublin, Ireland
Summary Six unusual cases diagnosed by various scientific methods are described to highlight the role of the histopathologist in clinical ophthalmology. The first case shows the importance of fast tissue diagnosis to prevent possible radical treatment in a limbal pseudotumour. The second presentation is of a small conjunctival mass with orbital involvement, immunohistochemically a B-cell lymphoma and occurring after a recent testicular tumour. The third patient presented with the rarely described nod ular hypersensitivity conjunctivitis (Splendore-Hoeppli reaction) and it is suggested that these ophthalmologically observed asymptomatic lesions are apparently clini cally transient so reports may be few because of infrequent biopsy. Pan-uveal melan ocytic tumours concurrent with thoracic or abdominal carcinoma are reviewed.
DNA flow cytometry could, perhaps, assess those ocular lesions for malignancy. The fourteenth case in the literature of lacrimal sac melanoma and possibly the first by tear seedling is illustrated. Lastly, a paediatric orbital fibrous histiocytoma is a cautionary anecdote with successful outcome.
I am very honoured to be chosen as the 4th European Guest Lecturer. I felt that I would take rare and interesting clinical ophthalmo logical conditions and illustrate the role of a histopathologist in their identification. Most of the cases described presented as space occupying lesions which, on microscopic examination, showed a wide variety of path ological reaction, with often an obscure aetiology. Management and prognosis where relevant are discussed. Firstly, three interesting conjunctival pro liferations are presented. Case Reports
(1) A 64 year old farmer was referred with a history of a sore red eye for seven months and of having had 'grit' removed by the local nurse, in the left eye 18 months pre-
viously following shaking straw. Vision was normal. On clinical examination there was a raised hard ridge of tissue above the limbus extending from 8 o'clock to 2 o'clock, with hyperaemia of the overlying and upper bulbar conjunctiva. No foreign body was demon strated on radiological examination. In view of the extent of the lesion and its consistency, carcinoma was considered a definite possi bility. A biopsy with frozen section control was proposed and, if positive, enucleation should follow. However, the patient refused enucleation. An excision biopsy was per formed. Histopathology of the small piece of tissue showed a chronic inflammatory lesion with fibroblasts sometimes in fascicular arrangement with many plasma cells and many eosinophils. The overlying conjunctival epithelium had undergone squamous meta-
European Guest Lecturer, Oxford Ophthalmological Congress, July,
1989.
Correspondence to: National Ophthalmic Pathology Laboratory & Registry of Ireland, Royal Victoria Eye & Ear Hospital, Adelaide Road, Dublin 2, Ireland.
80
Fig. 1
JOAN MULLANEY
Case 1. Limbal pseud otumour. (Courtesy of Mr Maurice Fenton)
plasia. The specimen was serially sectioned but no foreign body, fungus helminth or seed husk remnant could be identified. Malignancy was not found. This was an example of limbal pseudotumour with severe chronic inflam mation and architectural changes suggestive of fibrous histiocytoma. Three months later there was still some minor thickening and slight congestion. However, after eight years there is only a minute scleral scar at approxi mately 10 o'clock, in a white eye (Figs. 1 and 2). The case is presented to indicate the importance of the invocation of frozen sec tions examination during operation for the assessment of a large suspicious limbal lesion if enucleation is contemplated. (2) A 66 year old man presented with a left conjunctival nodule in July, 1988 and a history of orchidectomy in April, 1988 for seminoma. The conjunctival biopsy revealed itself to be a lymphomatous condition and, with histo chemistry, it was evident that it was a small B-celilymphoma. A month after the conjunc tival lesion he was referred to the orbital clinic with progressive downward displacement of
the left globe. A transeptal biopsy showe� that he now had a lymphoma (small B ce� type) occupying the upper temporal quadranV of the orbit. In view of the rarity of primary orbital lymt phomas his testicular biopsy was re-evaluated and the diagnosis was revised from that of seminoma to lymphoma (Fig. 3). He was referred to the Oncology unit and a full cr scan and bone marrow aspirate were normal. He was commenced on combination therapy BACOP/Bleomycin, Adriamycin, Cyclo phosphamide, Oncovin (Vincristin), and Pre dnisolone with six courses in all. The orbital lesion clinically resolved after four of the six courses. At the time of writing he is appar ently well. In this patient histopathology and histochemistry were important. The latter was used to re-evaluate the conjunctival, orbi tal and testicular lesions. The monoclonal markers, namely the common leucocyte anti gen (CLA) reliably marking 90% of the B cells identified in this case, can be done on paraffin sections. Placental leucocyte acid phosphatase (PLAP) (positive in seminoma)
PECULIAR OPHTHALMIC PROLIFERATIONS
Fig. 2
81
Case 1. Scar eight years after surgery.
was negative in the testicular, conjunctival and orbital lesions. This case is of consider able interest as seminoma histologically may resemble a lymphoma but treatment differs from that of a seminoma. (3) A 39 year old male patient had bilateral recurring dendritic ulcers from childhood which were quiescent. A routine examination in July 1983 showed small white nodules on the left bulbar conjunctiva underneath the upper lid with some hyperaemia (Fig. 4). After excision biopsy of these nodules he received chloromycetin ointment three times a day for a week. Histological examination of the nodules showed eosinophilic necrosis (Fig. 5) surrounded by epithelioid and mono nuclear cells with occasional giant cells of Langhan's type, numerous eosinophils as well as some plasma cells and lymphocytes. One month later two nodules reappeared. They were once again treated with chloromycetin and subsided. On 15 February 1984 the patient was seen with a similar nodule on the right conjunctiva which also regressed on treatment.
These findings conform to the hypersensi tivity reaction known as the Splendore Hoeppli phenomenon first described in the bulbar conjunctiva and well summarised by Ashton and Cook. I The eponyms arise from Splendore2 working in Brazil who described this reaction with a pulmonary fungus and Hoeppli3 in China who observed it with schistosoma ova. There is a slight air of des peration in the search for the causative agent of the rather typical histology. Bacteria (strep tococci), fungi, helminths, viruses, chlamydia trachomatis and even insects (warble fly) have been incriminated. The patient illustrated here had a long corneal herpetic history with treatment and the conjunctival nodules, never limbal, were apparently intermittent and causing no particular clinical disturbance. Case reports are extremely rare in the liter ature but discussions with numerous ophthal mologists would indicate that (a) these nodular proliferations are clinically not infre quently seen, (b) they may be asymptomatic, (c) hyperaemia can be slight, and (d) they seem to retrogress. The presence of numerous
82
Fig. 3
JOAN MULLANEY
Case 2. Testicular tubules with lymphomatous infiltration.
eosinophils suggests a hypersensitivity reac tion of as yet undetermined aetiology. Further studies are necessary to assess if this condition is of any real clinical significance when the aetiology is unknown or whether it is merely a passing pathological curiosity. Actinic granuloma has similar microscopic findings to the Splendore-Hoeppli phenom enon but there are no eosinophils. Swimming pool granuloma with marked injection of the conjunctiva caused by mycobacterium marinum is another histological differential diagnosis, but the organisms can be demon strated in the lesions. It sometimes imitates Parinauds ocular glandular syndrome. Next, problems relating to the melanocytic system will be considered. The vast literature on the pathology of the ocular pigmentary apparatus might suggest that the emergence of still obscure melan ocytic lesions would be unlikely, but interest ing facets can still be discovered. For example, free DNA was seen by light micro scopy in two necrotic choroidal melanomas4 in the form of lakes confirmed as being DNA by transmission electron microscopy and show-
ing a direct continuity between a lake and the nuclear chromatin. Jensen (personal com munication 1989) had not found DNA in mel anomas again. I have observed it in two specimens (Fig. 6). No other reports to date have appeared which is surprising in view of the common occurrence of necrotic uveal melanomas. The distribution of this free DNA in melanoma appears to differ from that found in retinoblastoma. An ultrastructural examination was found to be necessary to demonstrate the presence of small discrete electron dense DNA granules 60-200 nm in retinoblastoma.5 These deposits have an affin ity for collagen and basal lamina, especially in the iris and they were not phagocytosed by trabecular endothelial cells. Examination by transmission electron microscopy of the anterior segment in globes containing nec rotic uveal tract melanoma may give findings analogous to those found in retinoblastoma for free DNA deposition. DNA in tumours can be measured by flow cytometry. A comparison of nuclear/nucleo lar size in melanoma cells can be measured by allowing the nuclei, stained with a fluorescent
PECULIAR OPHTHALMIC PROLIFERATIONS
Fig.4
83
Case 3. Hypersensitivity nodular conjunctivitis (Splendore-Hoeppli phenomenon). Courtesy of Dr. Denis
Wilson. dye, to flow past a laser beam and the result
Retrospective studies by flow cytometry for
ing light emanations are plotted on a histo
ploidy abnormalities might be used to study
gram.6 This method can be used on paraffin
the pathological material from the eight cases
and retrospective studies are therefore poss
reported from 1966 to 19859-12 of a new syn
ible. Fresh specimens give more sensitive
drome with diffuse bilateral uveal melan
readings. Normal cells have a diploid comple
ocytic lesions and concurrent abdominal or
ment of DNA, ie two each of the autosomes
thoracic carcinomas. This is suggested as
but most tumour cells may be aneuploid with
there appears to be disagreement using light
increased numbers of chromosomes.
The
microscopic methods of examination on the
more aneuploid the tumour the worse the
enucleated specimens as to whether these rare
prognosis in melanomas. Ploidy abnormali
uveal tract lesions are naevi or melanomas (de
ties correlated with survival better than the
Wolff-Rouendaal, 1989 personal communica
usual histological parameters.7 However, in
tion). Six of the eight reported cases pre
contra distinction to melanomas large retino
sented first with increased visual loss but on
blastomas are said to have a normal ploidy
subsequent examination were found to have
level and this analytical method did not offer
information either about risk of metastases or
malignant epithelial tumours of pancreas, large intestine, lung, ovary and gall bladder.
the degree of anaplasia8 in these tumours. The
A general autopsy was performed on four
reasons for this are not understood and
patients but all eight cases had eyes studied
further analysis is necessary.
microscopically. The primary malignancy was
84
Fig.S
JOAN MULLANEY
Case 3. Histology eosinophilic necrosis with giant cells.
the cause of death. A 60 year old patient which we described13 had bilateral lens opac ities, left iris protrusion, macular elevation, patchy fluorescence and irregular fundal pig mentation
on
presentation.
After
three
months vision was reduced to hand move ments. There was rubeosis and extensive ret inal detachments. The patient
developed
in the literature of bilateral uveal malignant melanomas" and diffuse malignant melan omas are very rare14 and bilateral ocular car cinomatous metastases were uncommon in 10
of 196 eyes containing metastases.1S Further case descriptions are awaited with interest. Precancerous melanosis, classified under primary acquired melanosis by the W HO
disseminated intra-vascular coagulation and
group16 usually invokes a lively discussion
died. Ocular histopathology, post mortem,
about
showed diffuse pan uveal melanomata with an
patient with
occasional mitosis. Only one globe of the
multiple melanomata developed a very rare
reported cases was examined by transmission
complication.
electron
microscopy.
Melanosomes
microscopy
and
management.
precancerous
A
melanosis and
were
A 65 year old healthy man (normal vision)
identified in the lesions. The histopathology
presented in 1977 with a pigmented spot of
was most suggestive of melanoma and the
five years' duration under his right lower lid.
secondary effects on the globe were those of a
rapidly proliferating lesion. The differential diagnoses of these unusual ocular changes are
It was excised and was histologically a con junctival melanoma. During the next 11 years he had five other melanomata removed from
bilateral pigmented lesions on the fundus,
different lid and bulbar sites. Exenteration
bilateral hypertrophy of the pigment epithe
was contemplated but was decided against in
lium, toxic retinopathy, diffuse uveal malig
1981. He received chemotherapy in 1985.
nant
Epistaxis occurred in December 1988. He was
melanoma,
reactive
lymphoid multiple
admitted in January 1989 for exploration of
melanocytomas, metastatic disease or reticu lum cell sarcoma. 10 There are only 18 reports
the lacrimal sac where there was a hard black
hyperplasia,
leukemic infiltrates,
nodule filling the sac and involving the can-
85
PECULIAR OPHTHALMIC PROLIFERATIONS
Fig. 6
DNA 'lakes' in necrotic melanoma.
aliculus. This mass appeared to be a tumour
lacrimal sac. Thus, Blake and Mullaneyl8
and excision of lacrimal sac, canaliculi, naso
reported the fifth case of mucoepidermoid
lacrimal duct and medial and canthal liga
carcinoma at this site. The previous reports
ments were performed. Histology showed a
were two cases from Brazil19 and two cases
heavily pigmented poorly differentiated nec
from China.20 The incidence of mucoepider
rotic melanoma with extension into the neigh
moid carcinoma may be much greater than
bouring muscle. Serial sections failed to show
the literature indicates. A faulty diagnosis of
extension from conjunctiva. Ear, nose and
transitional cell carcinoma may frequently
throat examination showed nothing abnormal
have been made. Simple histochemical stains
in these cavities. At the time of writing his
for mucin can help to differentiate and this
right VA is
with good
can be further confirmed by transmission elec
closure of the lids. When he presented with
tron microscopy. Mucoepidermoid carcinoma
this last lesion he had conjunctival melanosis
carries a worse prognosis than the others at
but no tumour and it is postulated that this is
this region and exenteration is said to be the
either a new tumour arising in the lacrimal sac
procedure of choice in these cases.
6/24,
left VA is
6/9
from residual primitive melanin producing
Finally, the importance of accurate histo
cells developing in the sac during fetal ecto
pathological diagnosis in relation to an orbital
dermal downgrowth or a secondary seedling
tumour is demonstrated by the following
perhaps carried in by tears. Only 13 c�ses17 of
patient whom I presented at the 1978 Meeting
primary melanomas in the lacrimal sac have
of
been reported but these patients did not have
Society in view of the importance of the diag
precancerous melanosis. This would appear
nosis and of its rarity and a thirteen year fol
to be the fourteenth lacrimal sac melanoma
low-up can now be reported.21
and to be the first recorded in precancerous melanosis perhaps from a tear seedling. Other rarities may still be discovered in the
the
European
Ophthalmic
Pathology
A two year old girl had a swelling medial to her left eye which was said to have been pres ent since birth. She had mild proptosis,
86
JOAN MULLANEY
Fig. 7
Lacrimal sacfilled with melanoma.
normal vision and left optic disc swelling. Investigation indicated that she had an invas
comata or a metastases from an embryonal tumour enter as important differential diag
ive orbital tumour which, at surgery, was
noses if the patient is a child. Fibrous his
found to enter the ethmoid and nasal regions.
tiocytoma is extremely rare in infants and
The histological diagnosis was orbital fibrous histiocytoma. She had two recurrences at the
children. Our case appears to be the youngest ever diagnosed at that time in mid
1978 but
with chemotherapy. She is now fifteen years of
earlier that year a single case was recorded in a one year old child.22 An analysis of 150 cases
age. She has no epiphora,
of orbital fibrous histiocytoma had patients
age of three and eight years treated by surgery
5 mm of enophthal
mos, 4 mm of globe depression and normal ocular movements. VA right is
6/5,
left
6/12
ranging from four years of age upwards and·
the median was 43 years. 23 A single case of this
with slight left optic disc deformity. This case
tumour in a nine month old infane4 required.
illustrated very well the emphasis which must
ultrastructural
be put on accurate histopathological diagnosis in the management of this tumour. This girl,
and
immunohistochemical
studies, demonstrating the presence of vimen tin to distinguish the lesion from juvenile xan
now thirteen years after initial surgery for her
thogranuloma and eosinophilic granuloma
definitely invasive growth, appears still to be free of tumour. 21
derives from undifferentiated mesenchymae
Rhabdomyosarcoma, other soft tissue sar-
and the stem cells differentiate into fibroblasts
(histiocytosis
X).
Fibrous
histiocytoma
PECULIAR OPHTHALMIC PROLIFERATIONS
or histiocytes. This parentage may yield a wide range of histological findings both by light
microscopy,
transmISSIOn
electron
microscopy and immunohistochemistry and cause considerable confusion in the final diagnosis. The assessment of malignancy in fibrous histiocytoma can be difficult and may require sophisticated immunohistochemistry though even these findings are debatable. 23 Complete excision of the benign entity which is frequently locally invasive should be done while exenteration is recommended for cQn firmed malignant forms.22 Conclusion
This paper describes six cases of rare clinical aI)d pathological interest and contains cau tionary anecdotes. The material has been used to illustrate the necessity for the close liaison between ophthalmologists and pathol ogists in this field. Standard biopsy tissue
using light microscopy still yields the basic diagnosis in nearly all instances. The use of transmission electron microscopy to elucidate lesions, notably in the tumour area, c
